Our broad, long-term objectives are to supply reagents, models and expertise from a centralized Science Core facility to all participants of the Program. Core operation represents a balance between providing services based on established procedures, and continued innovation in methods and protocols. Safety is a particular guiding principle of the Core, and is are addressed by the many years of experience of Core participants in the study of TSEs, facilities for safe homogenization and other biohazard operating procedures, prion handling and decontamination. Protocol standardization is another crucial goal, so that all aspects of the Program have access to reagents and services produced and operated using consistent methods from a constant, reliable source. Specific Aims: Aim I - To supply purified recombinant PrP for assays to quantify prions, and for analyses of PrP conversion; Aim II - To supply purified anti-PrP monoclonal antibodies (mAbs) with well- defined properties; Aim III - To supply characterized transgenic and gene targeted mouse models; Aim IV - To quantify prions using sensitive, high throughput cell-based assays; and Aim V - To provide a variety of services to analyze pathological consequences of prion infection. The Science Core resides in outstanding environments for studies of prion diseases. Studies within individual Projects will be conducted in close collaboration with the Science Core to take advantage of the availability of models and expertise, standardized and consistent methodologies, and uniformly consistent, high quality reagents. The activity of the Core is essential for the successful accomplishment of Program goals.